The invention relates generally to a magnetic resonance spectroscopy (MRS) data acquisition technique and in particular to detection and monitoring of a neurodegenerative disease using this MRS technique.
The use of nuclear magnetic resonance spectroscopy data acquisition techniques for the determination of the presence and/or concentrations of individual chemical compounds is known as MR spectroscopy (MRS). Magnetic resonance spectroscopy is generally considered as a possible sensitive, non-invasive technique for detecting neurodegenerative diseases and monitoring therapy in such diseases. However, repeatability issues associated with the common spectroscopy techniques, as well as the inherent biological variability make the sensitivity/specificity of these techniques less than ideal in tracking metabolite changes due to disease or treatment.
Common spectroscopy techniques employed for neurodegenerative diseases detection and treatment monitoring generally include data acquisition protocols like STEAM (stimulated echo acquisition mode) and PRESS (Point RESolved Spectroscopy, a double spin echo imaging sequence). The spectra yielded by these two sequences are extremely complex, as all of the protons in the selected region of brain tissue produce a detectable signal. Consequently, it is difficult to reliably extract the concentration of every metabolite in the brain, and in particular the concentration of metabolites that change with disease and treatment. Therefore, relatively low sensitivity and specificity exist for MRS techniques in detecting early stages of a neurodegenerative disease such as Alzheimer disease (AD). AD is a progressive neurodegenerative disease, and even though its symptoms were first described almost a century ago, no definitive diagnostic exists even now. A “probable AD” diagnostic is usually given based on a series of neuropsychological, imaging and laboratory tests, only to ultimately be confirmed or infirmed (in ˜10% of the cases) through post-mortem pathological examinations. For example using existing MRS techniques, a patient may be classified as “probable” AD, that is, with a sensitivity (true positive rate) and specificity (false positive rate) for less than ideal (ideal numbers being 100% and 0%). Moreover, clinical studies that have used MRS as a marker for treatment efficacy involve a large number of subjects (treated and untreated) in order to show a statistically significant difference that could be assigned to the treatment.
Therefore there is a need for using more sensitive imaging or MRS techniques for detecting the metabolites of interest for early detection and treatment of a neurodegenerative disease in a patient. There is also a need to identify a suitable neuronal integrity marker that could be used as an indicator for the existence of the disease and follow its response to therapy in a timely fashion.